The Journal of Neuroscience, December 1, 2002, 22(23):10072-10077
BRIEF COMMUNICATION
Heterozygous Knock-Out Mice for Brain-Derived Neurotrophic Factor
Show a Pathway-Specific Impairment of Long-Term Potentiation But
Normal Critical Period for Monocular Deprivation
Alessandro
Bartoletti1, *,
Laura
Cancedda1, *,
Susan W.
Reid2,
Lino
Tessarollo2,
Vittorio
Porciatti3,
Tommaso
Pizzorusso1, 3, and
Lamberto
Maffei1, 3
1 Scuola Normale Superiore, Laboratorio di
Neurobiologia, 56100 Pisa, Italy, 2 Neural Development
Group, Mouse Cancer Genetics Program, National Cancer Institute,
Frederick, Maryland 21701, and 3 Istituto di Neuroscienze
Consiglio Nazionale delle Ricerche, Area Ricerca San Cataldo,
56100 Pisa, Italy
Genetic deletion of a single allele of the
BDNF gene affects hippocampal LTP and causes
several behavioral phenotypes, including deficits in spatial learning.
In the developing visual cortex, overexpression of BDNF accelerates the
time course of the critical period for monocular deprivation (MD), and
exogenous administration of BDNF alters the outcome of MD. We asked
whether reduced levels of BDNF could affect visual cortex plasticity by
studying long-term potentiation (LTP) induction and the effects of MD
in heterozygous BDNF knock-out mice. We found that theta burst
stimulation that induced LTP in the layer IV-III pathway of wild-type
(wt) mice caused only a transient potentiation in BDNF+/
mice, and
that this potentiation vanished in 25 min. In contrast, LTP elicited by
stimulation of the white matter (WM), a form of LTP that can be induced
only during the critical period, occurred normally in wt and BDNF+/
mice. The effects of MD during the critical period were similar in wt
and BDNF+/
mice, indicating that layer IV-evoked, layer III
LTP is not required for ocular dominance plasticity. We then asked
whether reduction of cortical BDNF levels could prolong the critical
period for MD and for the WM-evoked, layer III LTP induction. We found
that in adult BDNF+/
mice, WM-evoked, layer III LTP was not
inducible, and that the critical period for MD terminated normally. We
conclude that deletion of one copy of the BDNF gene
selectively impairs LTP of the layer IV-III pathway but does not alter
ocular dominance plasticity.
Key words:
ocular dominance; neurotrophins; LTP; visual cortex; TrkB; visual deprivation
*
A.B. and L.C. contributed equally to this paper.